Ischemic colitis of the colon in streptozotocin-induced diabetic rats.

This study focuses on two inflammatory diseases, viz., "diabetes mellitus (DM)" that causes serious complications such as retinopathy, nephropathy, and neuropathy, and "ischemic colitis" which is evoked by DM. Ischemic colitis originates from the reduction in mesenteric blood flow to the colon with existence of the occlusive or non-occlusive reasons. Our study objective was to provide early diagnostic approach for ischemic colitis in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were divided into four groups: (i) control use of 0.1 M citrate buffer, the solvent of streptozotocin (C), (ii). induced ischemia (I), (iii) rats subjected to 60 mg/kg STZ intraperitoneally to induce type 1 diabetes (D) (48 h after STZ injection, blood glucose levels >200 mg/dl were considered as diabetic), and (iv) diabetic rats subjected to intestinal ischemia (D+I). The third diabetic group (D) was not operated. At the end of the experimental period, rats were sacrificed, C-reactive protein (CRP) and calprotectin levels were measured in the serum and colon tissue specimens. Tissue specimens were also analyzed histologically. We found that serum and colon calprotectin levels were elevated in the D+I group compared to the D and/or I group alone, but relatively calprotectin levels increased in I as compared to C group in colon tissues. CRP levels were significantly increased with ischemic colitis in diabetes, while colon CRP levels were decreased. These results provide evidence for the existence of inflammation in the STZ-induced diabetic rats with ischemic colitis. In conclusion, our measurements of serum calprotectin levels of STZ-induced diabetic rats with ischemic colitis provide a practical approach for an early diagnosis of ischemic colitis. Furthermore, these biochemical analyses correlate well with the histopathologic findings of STZ-induced diabetic rats with ischemic colitis. Future studies would be desirable to further strengthen the role of calprotectin in the early diagnosis of ischemic colitis in diabetics clinical settings.

Tocilizumab's effect on cognitive deficits induced by intracerebroventricular administration of streptozotocin in Alzheimer's model.

Neuroinflammation plays pivotal roles in the pathogenesis of Alzheimer's disease (AD). IL-6 is pleiotropic cytokine which plays significant pathological role in inflammatory diseases and causes prolonged inflammation. Additionally, IL-6 activates microglia cells and enhances the accumulation of amyloid-ß peptides. Moreover, IL-6 signal transduction is mediated by membrane-bound and soluble IL-6 receptors. Tocilizumab which is a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody binds to both of these receptors and inhibits IL-6 signaling by this route. The objective was to investigate tocilizumab's potential effects in the treatment of AD. Male Sprague-Dawley rats were divided into three groups: sham (control), streptozotocin (STZ), and tocilizumab-STZ. We used a single dose of intracerebroventricular (ICV) tocilizumab, beginning 1 h prior to injection of STZ for 3 weeks. The rats in STZ and tocilizumab-STZ groups were given ICV-STZ (3 mg/kg). Behavioral parameters were evaluated on days 17-20 and the rats were sacrificed on day-21 to examine histopathological changes. STZ injection caused significant decrease in the mean escape latency in passive avoidance and also declined the performance improvement in Morris water maze tests. Tocilizumab-STZ group significantly improved learning and spatial memory functions by increasing RLT in the passive avoidance and by shortening escape latency in reaching the platform in the Morris water maze. Histopathological changes were examined using hematoxylin and eosin and immunohistochemical (IHC) stainings. IHC analysis revealed that while protein expressions of amyloid-ß (3.5 ± 0.2) and IL-6 (2.9 ± 0.4) showed intense immune-positivity in STZ group, amyloid-ß (1.3 ± 0.1) and IL-6 (1.5 ± 0.2) immunoreactivities were substantially decreased in tocilizumab treatment group. We conclude that tocilizumab treatment attenuated significantly STZ-induced cognitive impairment and histopathological changes. Further studies would be desirable to investigate clinically relevant protective effects of tocilizumab in AD.

A study comparing the effects of rosiglitazone and/or insulin treatments on streptozotocin induced diabetic (type I diabetes) rat aorta and cavernous tissues.

Our aim was to investigate the role of oxidative stress and inflammation on the functional and biochemical changes caused by hyperglycemia in the aorta and corpus cavernosum tissues of streptozotozin diabetic rats and to determine if rosiglitazone and/or insulin treatment has any preventive effect on organ dysfunction. Wistar Albino rats were divided into 2 groups. I) Control group: a) Vehicle, 0.1 M citrate buffer, the solvent of streptozotocin injected intraperitoneally (i.p) and b) Rosiglitazone group: (4 mg/kg/day, i.p.) for 8 weeks. II) Diabetic group: streptozotocin (60 mg/kg) was administered i.p. to induce diabetes. 48 h after streptozotocin injection, animals were divided into 4 subgroups (n=6 for each group); a) no treatment group (D), b) treated with rosiglitazone (4 mg/kg/day) (DR), c) treated with insulin (6 U/kg/day) (DI) and d) treated with insulin and rosiglitazone (DRI) for 8 weeks. At the end of the experimental period, animals were decapitated and tissue samples were collected for in vitro experiments and biochemical studies. Endothelium dependent relaxation induced by acetylcholine in the aorta and corpus cavernosum tissues were attenuated in the diabetic group, whereas phenylephrine induced contractile responses were reduced. These responses were restored after rosiglitazone and/or insulin treatment, the combination being the most efficient treatment. Malondialdehyde and TNF-α levels were increased in diabetic rats while glutathione levels were decreased. All treatments prevented these changes in biochemical parameters, rosiglitazone and insulin combination again being the most efficient treatment. Our results suggested that supplementing diabetic patients receiving insulin treatment with adjunct therapy of rosiglitazone may have some benefit for controlling diabetic complications.